The neurological and musculo-skeletal manifestations of Chagas' disease will continue to be the major focus of our laboratory's efforts in the next 3-5 years. Using murine and human neuroblastoma cells (PC12, NS20Y, LAN series) we will study the cellular and molecular basis of the pathogenesis as well as late Chagas' disease. We will determine the effect of parasitism on important biochemical markers such as choline acetyltransferase (CAT), acetylcholinesterase (AchE), somatostatin, nicotinic and muscarinic acetylcholine receptors, and various neurotransmitters such as norepinephrine, dopamine, serotonin, and their metabolites. The effect of Trypanosoma cruzi infection on other aspects of cell function such as differentiation of precursor cells to terminally differentiated neurons will be studied in the unique PC12 cell line using parameters such as infectivity, morphology and biochemistry. Our laboratory will continue to utilize the L6E9 muscle cell line as well as the rodent in vivo model to determine the effect of T. cruzi infection on the Beta-receptor cAMP complex. In this regard we will determine the specific locus of action of T. cruzi (i.e. receptor unit, coupling unit, or catalytic unit). These studies will have profound implications for the pathogenesis of the neurological cardiological manifestations of Chagas' disease. An understanding of the molecular events that attend infection may ultimately lead to pharmacologic intervention which may reverse the physiological abnormalities.